Potent and systematic RNAi mediated silencing with single oligonucleotide compounds
- Jennifer Lapierre1,
- William Salomon1,2,
- James Cardia,
- Karen Bulock,
- Jessica T. Lam,
- William J. Stanney,
- Glenna Ford,
- Bernice Smith-Anzures,
- Tod Woolf,
- Joanne Kamens,
- Anastasia Khvorova and
- Dmitry Samarsky
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↵1 These authors contributed equally to this work.
Abstract
RNA interference (RNAi) has been established as an important tool for functional genomics studies and has great promise as a therapeutic intervention for human diseases. In mammalian cells, RNAi is conventionally induced by 19–27-bp RNA duplexes generated by hybridization of two complementary oligonucleotide strands (oligos). Here we describe a novel class of RNAi molecules composed of a single 25–28-nucleotide (nt) oligo. The oligo has a 16-nt mRNA targeting region, followed by an additional 8–10 nt to enable self-dimerization into a partially complementary duplex. Analysis of numerous diverse structures demonstrates that molecules composed of two short helices separated by a loop can efficiently enter and activate the RNA-induced silencing complex (RISC). This finding enables the design of highly effective single-oligo compounds for any mRNA target.
Keywords
Footnotes
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Reprint requests to: Dmitry Samarsky, RXi Pharmaceuticals Corporation, Gateway Life Sciences Park, 60 Prescott Street, Worcester, MA 01605, USA; e-mail: dsamarsky{at}rxipharma.com; fax: (508) 767-3862.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.2399411.
- Received August 2, 2010.
- Accepted March 3, 2011.
- Copyright © 2011 RNA Society
